Individual risk prediction of node and distant metastasis based on lymphangiogenic intensity in typical pulmonary carcinoid tumor / Predição do risco individual de metástase linfática e hematogênica em função da intensidade da linfangiogênese no tumor carcinóide típico broncopulmonar

AUTOR(ES)

Mariana Tosello Laloni

DATA DE PUBLICAÇÃO

2008

RESUMO

Typical pulmonary carcinoids are neuroendocrine cells proliferations and they were former considered lung adenomas with no hematogenic or lymphatic metastatic potential. However, it is known that up to 20% of patients develop metastatic disease. It is mandatory that new studies be developed due to the variation in clinical presentation of these patients. It is also required that the individual risk of lymphatic and hematogenic metastasis be determined in order to individualize the patients treatment. Pulmonary carcinoids are classified according to hystologic grade. The current classification includes hystologic grade, presence or absence of necrosis, nuclear pleomorphism, and vascular invasion. This classification is based on Hematoxylin and Eosin stain and this technique can not assess biomolecular processes related to malignant potential. Trying to identify the malignant potential of the carcinoid tumors some studies have already been designed to identify some proteins as PCNA, p53, Ki-67, apoptosis proteins (Bcl-2, Bax and Bak), collagen and elastic fibers as well as angiogenic process. However, the lymphangiogenic mechanism has never been evaluated in typical pulmonary carcinoid tumors. Recently some molecules (VEGF-C, VEGFR-3 and LYVE-1) that are specifically expressed in the endothelium of the lymphatic vessels have been identified. These findings have improved the lymphangiogenic mechanism comprehension. This study used the immunohistochemical technique to identify VEGF-C, VEGFR-3 and LYVE-1 in 182 patients submitted to surgical procedures to treat Typical pulmonary carcinoid tumors. Lymphatic metastasis were diagnosed in 23 of 182 patients and 17 of 182 patients were identified with hematogenic metastasis. Futhermore, this study was the first reported one which has tried to quantify the lymphatic vessels using the LYVE-1 as an immunohistochemical marker. This study could not assess VEGF-C and VEGFR-e expression in Typical pulmonary carcinoids since an internal negative control could not be determined. There was a statistical difference between the median age and gender. There was no statistical difference between the median diameter and the number of positive lymph nodes related to the gender. This study demonstrated a statistical difference between the diameter and positive margins related to the group of patients that have developed metastatic disease and the group of patients with no metatastatic disease. There was no difference between the group of patients that have developed metastatic disease and the group of patients with no metatastatic disease according to the median number of lymphatic vessels stained. Based on logistic regression this study demonstrated that there is a predictive risk of developing hematogenic metastasis related to the diameter of the tumor. The predictive risk of the lymphatic metastasis was not improved by the number of the immunohistochemical stained lymphatic vessels, according to the logistic regression model. The immunohistochemical expression of LYVE-1 has not demonstrated statistical correlation between the parameters studied. Other than immnuhistochemical techniques are required to improve the comprehension of the lymphangiogenic mechanism involved in the Typical pulmonary carcinoid tumor

ASSUNTO(S)

risk factor neoplasias brônquicas/classificação lymphatic vessel neuroendocrine tumors/classification vasos linfáticos bronquial neoplasms/classification marcadores biológicos de tumor/classificação linphangiogeneses tumour biomarkers/classification linfagiogênese carcinoid tumors/classification tumores neuroendócrinos/classificação metástase neoplásica metastasis tumor carcinóide/classificação carcinoma neuroendócrino/ classificação fatores de risco neuroendocrine carcinoma/classification

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